Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management A Randomized Clinical Trial
Clinically Significant Bleeding With Ticagrelor Versus Clopidogrel in Korean Patients With Acute Coronary Syndromes Intended for Invasive Management A Randomized Clinical Trial
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DOI：
10.1161/circulationaha.119.041766
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发表时间：
2019-12-03
期刊：
影响因子：
37.8
通讯作者：
Park, Seung-Jung
中科院分区：
文献类型：
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作者：
Park, Duk-Woo;Kwon, Osung;Park, Seung-Jung
背景资料：由于对抗血小板治疗有反应的出血和缺血事件的不同倾向，强效P2 Y12抑制剂替格瑞洛在东亚人群中的安全性和有效性仍不确定。研究方法：在这项多中心试验中，800名因急性冠状动脉综合征（伴或不伴ST段抬高）住院并打算进行侵入性管理的韩国患者以1：1的比例随机分配接受替格瑞洛（180 mg负荷剂量，此后90 mg每日两次）或氯吡格雷（600 mg负荷剂量，此后75 mg每日一次）。主要安全性结局为12个月时具有临床意义的出血（根据PLATO（血小板抑制和患者结局）标准，大出血或轻微出血的复合终点）。结果如下：在12个月时，替格瑞洛组的临床显著出血发生率显著高于氯吡格雷组（11.7% [45/400] vs 5.3% [21/400];风险比[HR]，2.26; 95%置信区间[CI]，1.34 - 3.79; P=0.002）。替格瑞洛组的大出血（7.5% [29/400] vs 4.1% [16/400]，P=0.04）和致死性出血（1% [4/400] vs 0%，P=0.04）的发生率也较高。替格瑞洛组和氯吡格雷组之间心血管原因、心肌梗死或卒中导致的死亡发生率无显著差异（9.2% [36/400] vs 5.8% [23/400]; HR，1.62; 95% CI，0.96 - 2.74; P=0.07）。使用几种不同的分析方法和多个亚组的总体安全性和有效性结果相似。结论：在打算接受早期侵入性治疗的韩国急性冠状动脉综合征患者中，与氯吡格雷相比，标准剂量的替格瑞洛与临床显著出血的发生率较高相关。鉴于本试验的效力不足，无法得出任何有关疗效的结论，因此应谨慎解释缺血性事件发生率在数值上较高的情况。
Background: Owing to the differential propensity for bleeding and ischemic events with response to antiplatelet therapy, the safety and effectiveness of potent P2Y12 inhibitor ticagrelor in East Asian populations remain uncertain. Methods: In this multicenter trial, 800 Korean patients hospitalized for acute coronary syndromes with or without ST elevation and intended for invasive management were randomly assigned to receive, in a 1:1 ratio, ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (600 mg loading dose, 75 mg daily thereafter). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to PLATO (Platelet Inhibition and Patient Outcomes) criteria at 12 months. Results: At 12 months, the incidence of clinically significant bleeding was significantly higher in the ticagrelor group than in the clopidogrel group (11.7% [45/400] vs 5.3% [21/400]; hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.34 to 3.79; P=0.002). The incidences of major bleeding (7.5% [29/400] vs 4.1% [16/400], P=0.04) and fatal bleeding (1% [4/400] vs 0%, P=0.04) were also higher in the ticagrelor group. The incidence of death from cardiovascular causes, myocardial infarction, or stroke was not significantly different between the ticagrelor group and the clopidogrel group (9.2% [36/400] vs 5.8% [23/400]; HR, 1.62; 95% CI, 0.96 to 2.74; P=0.07). Overall safety and effectiveness findings were similar with the use of several different analytic methods and in multiple subgroups. Conclusions: In Korean acute coronary syndrome patients intended to receive early invasive management, standard-dose ticagrelor as compared with clopidogrel was associated with a higher incidence of clinically significant bleeding. The numerically higher incidence of ischemic events should be interpreted with caution, given the present trial was underpowered to draw any conclusion regarding efficacy.